Various Cytokines Modulate ICAM-1 Shedding on Melanoma- and CTCL-Derived Cell Lines: Inverse Regulation of ICAM-1 Shedding in a Sézary Cell Line by Interferon-γ

Abstract

Background: Since soluble intercellular adhesion molecules 1 (sICAM-1) retain their ability to bind to their ligand, they can interfere in cell-mediated immunosurveillance. Objective: We studied the impact of various cytokines on ICAM-1 release of several tumor cell lines. Methods: Two melanoma cell lines (M19, M26), 1 B lymphoblastoid cell line (Daudi), 1 erythroleukemia cell line (K562), 1 Sézary-cell-derived cell line (SeAx), 1 cell line derived from a mycosis fungoides lesion (MyLa) and normal peripheral blood mononuclear cells (PBMC) were grown in the presence of interferon γ (IFN-γ), IFN-α, interleukin-2 (IL-2), IL-6 and tumor necrosis factor α (TNF-α) in various concentrations. ICAM-1 release into the supernatant was measured after 24 and 48 h using an enzyme-linked immunosorbent assay (ELISA). Results: PBMC and the B lymphoblastoid cell line did not shed detectable amounts of sICAM-1. In all other cell lines, ICAM-1 shedding was found with and without cytokine stimulation. In all cell cell lines except the CTCL-derived one, ICAM-1 shedding was marginally affected by IFN-α, IL-2 and IL-6. TNF-α and IFN-γ enhanced the shedding in a time- and dose-dependent manner. In the SeAx line, IL-2 and IFN-γ inhibited ICAM-1 release. By contrast, TNF-α and IL-6 enhanced it. The CTCL-derived MyLa responded to IFN-α with a dose-dependent increase in ICAM-1 shedding. All other cytokines had marginal influence. Conclusion: Cytokine-modulated ICAM-1 shedding shows quantitative and qualitative differences in the investigated cell lines. This might have implications for the pathophysiology of cutaneous malignancies and their susceptibility to immunotherapies.

Soluble ICAM-1 secretion and its functional role as an autocrine growth factor in nasal NK/T cell lymphoma cells

“…Although previous studies have reported sICAM-1 secretion in vitro in several cell lines [14][15][16][17][18] and highly significant sICAM-1 levels in patients' sera in a wide variety of malignancies [18][19][20], the functional role of soluble ICAM-1 is yet to be completely understood. To the best of our knowledge, the present study is the first to show that sICAM-1 has a functional role as an autocrine growth factor for neoplastic cells.…”

“…ICAM-1 is constitutively expressed on a limited number of tissues, but is induced in a wide variety of normal cells such as vascular endothelial cells, leukocytes, and some epithelial tissues [13]. Soluble ICAM-1 (sICAM-1) secretion in vitro was previously reported in cell lines derived from melanoma, lymphoma, and renal carcinoma [14][15][16][17][18]. In addition, highly significant sICAM-1 levels were reported in the sera from patients suffering from different malignancies [18][19][20].…”

Inverse regulation of neuronal cellular adhesion molecule (NCAM) by IFN-? in melanoma cell cultures established from CNS lesions

“…Thus, shedding of ICAM‐1 may be one of the mechanisms by which neoplastic cells escape immunosurveillance. Shedding of ICAM‐1 is strongly enhanced upon stimulation by IFN‐γ (Dummer et al, 1994).…”